Optically active 2-hydroxycarboxylic acids are useful compounds as reagents or raw materials in the manufacture of medicines, agrochemicals, and industrial products. For example, 2-hydroxycarboxylic acid can be used as an important raw material of (R)-2-(3-{N-(benzoxazol-2-yl)-N-[3-(4-methoxyphenoxy)propyl]aminomethyl}phenoxy)butyric acid of the following formula that is a selective PPARα-activating agent and is useful as a preventive and/or a therapeutic agent for hyperlipidemia, arteriosclerosis, diabetes, diabetes complications, inflammation, and cardiac disorders (Patent Document 1). In the manufacture of the above-described compound, optical purity of 2-hydroxybutyric acid serving as a synthesis intermediate, or a derivative thereof directly and considerably affects optical purity of the final product. Therefore, a pharmaceutical ingredient having higher optical purity is desired (Patent Documents 2 to 6).

Such an optically active 2-hydroxybutyric acid derivative is, commercially available (Aldrich), but very expensive. Hitherto, there have been known several methods for manufacturing optically active 2-hydroxycarboxylic acid ester derivatives as shown in the following reaction schemes:
(1) Method for manufacturing an optically active 2-hydroxybutyric acid ester by asymmetric reduction of 2-keto butyric acid ester using a baker's yeast (Non-Patent Document 1),
(2) Method for manufacturing an optically active 2-hydroxybutyric acid ester using L-methionine as a starting material (Non-Patent Documents 2 and 3),
(3) Method for manufacturing an optically active 2-hydroxycarboxylic acid ester derivative by asymmetric reduction of an acrylic acid derivative (Non-Patent Document 4), and
(4) Method for manufacturing an optically active 2-hydroxycarboxylic acid derivative using an aldehyde as a starting material via optically active cyanohydrin (Patent Document 7).

However, in method (1), the optical purity (S configuration) and the chemical yield of the resultant 2-hydroxybutyric acid ester are 75% e.e. and 42% respectively when free baker's yeast is used, and are 66% e.e. and 42% respectively when immobilized baker's yeast is used. Therefore, neither of them is suitable for manufacturing a 2-hydroxybutyric acid ester with high optical purity. Thus, method (1) is not an industrially available manufacturing method. In addition, a 2-keto butyric acid ester is chemically unstable and is expensive, which is problematic. Furthermore, optically active 2-hydroxycarboxylic acid ester having R configuration cannot be yielded through method (1).
In method (2), a target optically active 2-hydroxybutyric acid ester can be manufactured using inexpensive L-methionine as a starting material. However, three steps are required for the manufacture of the target product, and the total yield is as low as 32%. Furthermore, method (2) is not efficient, since, for example, a large amount of solvent is required for the reaction and post-treatment of reaction. Also, since the manufacturing method involves a step of forming an unstable diazonium salt, it is difficult to control the reaction conditions. As a result, consistent yield and optical purity of the target product may not be obtained, and the optical purity may be significantly lowered depending on the manufacturing scale.
In method (3), a target product having high optical purity can be yielded through asymmetrically reducing double bonds in a 2-acyloxyacrylic acid ester derivative through hydrolysis with acid in the presence of an asymmetric catalyst. However, cumbersome operations are required for producing a 2-acyloxyacrylic acid ester derivative serving as a starting substrate. In addition, method (3) is not an industrially advantageous manufacturing method, involving problems such as preparation of an expensive asymmetric ligand and carrying out reduction under high pressure hydrogen.
In method (4), a 2-hydroxy carboxylic acid derivative is manufactured in two steps, i.e., conversion of an aldehyde into asymmetric cyanohydrin and subsequent hydrolysis. This requires a cumbersome preparation of an asymmetric ligand serving as an asymmetric catalyst. With regard to optical purity, the optical purity and the chemical yield of the target are likely to vary depending on the substituent of the reaction substrate.
In a known alternative method, racemic 2-hydroxy butyric acid is transformed into a corresponding diastereomer salt by using brucine, and the salt is subjected to optical resolution (Non-Patent Document 5). The document does not disclose optical purity. Also reported is a kinetic optical resolution of 2-hydroxycarboxylic acid by using recombinant E. coli (Non-Patent Document 6). However, the method is not industrially practical.
Furthermore, it is reported the optical purity of an inorganic salt of 2-hydroxyhexanoic acid (Non-Patent Document 7). However, it is not known that a 2-hydroxycarboxylic acid having high optical purity and a derivative thereof can be produced from the thus-formed inorganic salt.